I will study the mechanism of lung microvascular injury which develops after pulmonary air embolization by identifying ultrastructurally the site of increased microvascular permeability and correlating these structural observations temporally with functional variables during injury and recovery processes. I will define the association between neutrophil sequestration and pulmonary microvascular injury, study the role of neutrophils, platelets and fibrinogen in the injury process by specific depletion experiments and compare the fine structure of neutrophils before and after lung injury. The experiments will be done in anesthetized and unanesthetized sheep by infusing air bubbles intravenously to embolize the lungs. Lung lymph flow and hemodynamics will be monitored in each animal to correlate function with structure. In future experiments, the morphologic effects of pulmonary microvascular air embolization will be compared with the ultrastructural responses to several other substances in order to determine if a "final common pathway" is shared among different injurious agents in sheep. This approach will result in the better understanding of the pathology and pathophysiology of the sheep respiratory distress syndrome which may lead to suggested therapies or preventive treatments for clinical problems.